In the process of tuning each section of the mass spectrometer in a liquid chromatograph mass spectrometer (LC/MS), a sample which contains known kinds of components at known concentrations is used (such a sample is generally called a calibration sample, a standard sample or the like). The “tuning” is the task of optimally setting control parameters related to various analysis conditions (such as the voltages applied to various elements, the temperature of the ionization probe, and the gas flow rate) in order to calibrate the mass-to-charge ratio m/z, adjust the mass-resolving power, regulate the sensitivity or for other purposes. During the tuning process, the signal intensity of an ion originating from a target component in a sample is monitored while the value of a control parameter to be adjusted is sequentially changed, so as to search for a parameter value at which the signal intensity is maximized. Since such a process of finding an optimal value of a control parameter requires a certain amount of time, an infusion method has conventionally and generally been used for the introduction of a sample into an ion source. The infusion method is a technique in which a liquid sample is continuously introduced into an ion source through a syringe pump or similar device. Although this technique ensures a stable analysis for a comparatively long period of time, a drawback exists in that it consumes a large amount of the sample.
By contrast, a flow injection method is a technique in which a preset amount of sample is injected through some device (e.g. an injector for a liquid chromatograph) into a mobile phase supplied at a constant flow rate, thus having the sample be carried into the ion source by the flow of the mobile phase (for example, see Patent Literature 1). In the FIA method, the amount of sample used is much smaller than in the infusion method. However, the flow injection method has the problem that the period of time in which the sample is introduced into the ion source is short, and furthermore, the concentration of the target component shows a hill-shaped change with time. Therefore, when the flow injection method is used to introduce a sample for tuning the system, a stricter timing arrangement is required on the data collection than in the case of using the infusion method.
Hereinafter described as one example of the system-tuning process is the case of optimizing a collision energy for the collision-induced dissociation (CID) of ions in a triple quadrupole mass spectrometer capable of an MS/MS analysis. The amount of collision energy possessed by the ions in the CID depends on a voltage applied between the collision cell and the ion optical element (e.g. an ion guide or a front-stage quadrupole mass filter) provided before the collision cell. Accordingly, adjusting the collision energy actually means adjusting a voltage (which is hereinafter called the “collision-energy voltage”).
In general, even if the kind of ions is the same, the form of fragmentation of the ions caused by CID changes depending on the collision energy. Therefore, even if the same kind of precursor ion is chosen as the CID target, the optimal value of the collision-energy voltage changes depending on the target product ion (to be analyzed). Accordingly, in a multiple reaction monitoring (MRM) measurement or a similar mode of MS/MS analysis in which the mass-to-charge ratio of the product ion is fixed, if there are a plurality of kinds of target product ions, it is necessary to search for the optimal value of the collision-energy voltage for each product ion.
Patent Literature 2 discloses a conventionally known method for detecting the ion intensity of each of the product ions generated by fragmentation of a predetermined precursor ion under a plurality of previously set collision-energy voltages. In this analyzing method, the ion intensity of each product ion is obtained at different collision-energy voltages by repeatedly performing a cycle of analyses which cover all the possible combinations of the collision-energy voltages and the kinds of product ions.
In the method of exhaustively obtaining ion intensities in the previously described manner, if there is no information about an appropriate range of the collision-energy voltage, it is necessary to measure the ion intensity of each product ion over a considerably wide range of collision-energy voltages while sequentially changing the voltage value in comparatively small steps. In such a case, the data must be obtained at a considerable number of points in each cycle, so that each cycle requires a long period of time if the intervals of time for data obtainment is maintained. As explained earlier, in the flow injection method, the concentration of a component in a sample introduced into the ion source shows a hill-shaped change, which makes it difficult to find an optimal value of the collision-energy voltage based on the result of a single cycle of analyses. Therefore, it is necessary to accumulate ion intensities over a few to several cycles of analyses in order to find an optimal value of the collision-energy voltage. If each cycle requires a long period of time as in the previously described case, it is extremely difficult to find the optimal value while the target component is being introduced into the ion source. As a result, the same analysis needs to be performed a plurality of times for the same sample, which consumes a greater amount of the sample and requires a longer period of time for the tuning.
This problem is particularly noticeable in the case of the flow injection method, in which the sample injection period is limited. However, the infusion method also has a similar problem in that the period of time for the tuning becomes longer and the amount of sample consumed becomes larger with an increase in the number of times of the operation of measuring the ion intensity while changing the collision-energy voltage.
The previously described problem is not specific to the optimization of the collision-energy voltage but is common to any control parameters that need to be optimized in mass spectrometers, such as the lens voltage applied to an ion lens, the flow rate of a nebulizing gas or a drying gas used in an ion source which employs an electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI) or similar technique, the heating temperature of the ion source, the temperature of a heated capillary for transporting the generated ions from the ion source to the subsequent stage, and the laser intensity in the case where an atmospheric pressure photoionization (APPI) source is used.